Transition in Survival From Low-Dose Hyper-Radiosensitivity to Increased Radioresistance Is Independent of Activation of ATM SER1981 Activity

Krueger, S.A.; Collis, Spencer J.; Joiner, Michael C.; Wilson, George D.; Marples, Brian

doi:10.1016/j.ijrobp.2007.08.012

Cited by 76 publications

(72 citation statements)

References 36 publications

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“…1). Although the reasons for the absence of HRS in some cells are not well understood, it has been suggested that HRS-negative cell lines have a dissociation between ataxia telangiectasia mutated (ATM) activity and early G 2 -phase checkpoint function, producing an aberrant early G 2 -phase checkpoint response that evades dose-dependent ATM regulatory control (31). However, H460 cells did not show any G 2 -phase arrest after LDFRT (Fig.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Fractionated Radiation Potentiates the Effects of Cisplatin Independent of the Hyper-Radiation Sensitivity in Human Lung Cancer Cells

Gupta

Koru‐Sengul

Arnold

et al. 2011

Molecular Cancer Therapeutics

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In this study, the role of hyper-radiation sensitivity (HRS) in potentiating the effects of cisplatin by low-dose fractionated radiation (LDFRT) was evaluated in four human non-small cell lung cancer cell lines. Presence of HRS and cisplatin enhancement ratio (CER) by LDFRT/2 Gy was assessed using colony-forming and apoptotic assays. Cell-cycle disturbances were studied by flow cytometry. Expression of genes involved in apoptosis was assessed using real-time reverse transcriptase PCR arrays. H-157 cells showed a distinct HRS region, followed by UKY-29 and A549 cells, whereas it was absent in H460 cells, which when lack HRS showed maximum CER with LDFRT (4 Â 0.5 Gy) both by clonogenic inhibition and by apoptosis compared with single fraction of 2 Gy whereas the most radioresistant A549 cells had the least CER, with no significant differences between LDFRT or 2 Gy. Interestingly, in H-157 cells, a more pronounced CER was observed with LDFRT when assessed by apoptosis but clonogenic inhibition-CER was higher with 2 Gy than with LDFRT. Excluding H-157 cells, the CER by LDFRT was inversely proportional to radioresistance [(determined by D 0 , the dose to reduce survival by 67% from any point on the linear portion of the survival curve or surviving fraction (SF) at 2 Gy (SF 2 )] of the cells. LDFRT alone or in combination with cisplatin induced larger number of proapoptotic genes than 2 Gy or cisplatin þ 2 Gy in cells showing HRS when compared to H460 cells that lack HRS. These findings indicate that chemopotentiation by LDFRT is correlated more with the intrinsic radiation sensitivity of the non-small lung cancer cells than the HRS phenomenon whereas the mode of cell killing is both through apoptosis and clonogenic inhibition. Mol Cancer Ther; 10(2); 292-302. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

Low-Dose Fractionated Radiation Potentiates the Effects of Cisplatin Independent of the Hyper-Radiation Sensitivity in Human Lung Cancer Cells

Gupta

Koru‐Sengul

Arnold

et al. 2011

Molecular Cancer Therapeutics

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“…Accumulated evidence has suggested that cell cycle may function as a regulatory process in radioresistance. Krueger et al have showed that abrogation of the checkpoint by inhibition of checkpoint kinase 1 (Chk1) and checkpoint kinase 2 (Chk2) increased lowdose radiosensitivity (Krueger et al, 2007). In metastatic brain tumors,the expression levels of phosphorylatedChk1 proteins tend to be higher in radioresistant cancer than in radiosensitive cell lines (Seol et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Involvement of Cdc25c in Cell Cycle Alteration of a Radioresistant Lung Cancer Cell Line Established with Fractionated Ionizing Radiation

Li¹,

Yang²,

Mei³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Cancer patients often suffer from local tumor recurrence after radiation therapy. Cell cycling, an intricate sequence of events which guarantees high genomic fidelity, has been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. Here, we established a radioresistant lung cancer cell line, A549R , by exposing the parental A549 cells to repeated γ-ray irradiation with a total dose of 60 Gy. The radiosensitivity of A549 and A549R was confirmed using colony formation assays. We then focused on examination of the cell cycle distribution between A549 and A549R and found that the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased. When A549 and A549R cells were exposed to 4 Gy irradiation the total differences in cell cycle redistribution suggested that G2-M cell cycle arrest plays a predominant role in mediating radioresistance. In order to further explore the possible mechanisms behind the cell cycle related radioresistance, we examined the expression of Cdc25 proteins which orchestrate cell cycle transitions. The results showed that expression of Cdc25c increased accompanied by the decrease of Cdc25a and we proposed that the quantity of Cdc25c, rather than activated Cdc25c or Cdc25a, determines the radioresistance of cells.

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“…It is important to note that LDHRS has not been observed for high-linearenergy-transfer radiations (such as neutrons) [2,16], and this indicates that reparation plays an important role. It has also been suggested that the repair induction is a consequence of the fact that the cell cycle is stopped in the G2 phase, because this permits the cell to repair the lesions produced before it divides, and this only occurs for a given threshold dose [18][19][20]. According to several authors [21][22][23], this links LDHRS with the so-called dose rate inverse effect [24,25].…”

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confidence: 99%

Low-dose radiation hyper-radiosensitivity in multicellular tumour spheroids

Guirado¹,

Aranda²,

Ortiz³

et al. 2012

BJR

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Objective: We propose and study a new model aimed at describing the low-dose hyperradiosensitivity phenomenon appearing in the survival curves of different cell lines. Methods: The model uses the induced repair assumption, considering that the critical dose at which this mechanism begins to act varies from cell to cell in a given population. The model proposed is compared with the linear-quadratic model and the modified linear-quadratic model, which is commonly used in literature and in which the induced repair is taken into account in a heuristic way. The survival curve for the MCF-7 line of human breast cancer is measured at low absorbed doses and the uncertainties in these doses are estimated using thermoluminiscent dosemeters. Results: It is shown that these multicellular spheroids present low-dose hyperradiosensitivity. The new model permits an accurate description of the data of two human cell lines (previously published) and of the multicellular spheroids of the MCF-7 line here measured. Conclusion: The model shows enough flexibility to account for data with very different characteristics and considers in a faithful way the hypothesis of the repair induction.

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Transition in Survival From Low-Dose Hyper-Radiosensitivity to Increased Radioresistance Is Independent of Activation of ATM SER1981 Activity

Cited by 76 publications

References 36 publications

Low-Dose Fractionated Radiation Potentiates the Effects of Cisplatin Independent of the Hyper-Radiation Sensitivity in Human Lung Cancer Cells

Low-Dose Fractionated Radiation Potentiates the Effects of Cisplatin Independent of the Hyper-Radiation Sensitivity in Human Lung Cancer Cells

Involvement of Cdc25c in Cell Cycle Alteration of a Radioresistant Lung Cancer Cell Line Established with Fractionated Ionizing Radiation

Low-dose radiation hyper-radiosensitivity in multicellular tumour spheroids

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